It is proposed to investigate a group of soluble glycoproteins that are prominent extracellular constituents of the goldfish CNS and show enhanced expression during regeneration of the goldfish optic nerve. We have found that these "exoglycoproteins" (XGPs) are associated with lipid and bind to heparin, properties that also occur in some molecules important in neuronal development and regeneration. Moreover, these properties suggest the possibility of some connection with the immune system. We have also detected XGPs or related proteins in cells of the optic nerve and brain of neonatal rats, which suggests that they may play a role in development of the central nervous system of mammals as well as in regeneration of neurons in goldfish. The objectives of the proposed experiments are to characterize the XGPs in the optic nerve and tectum of the goldfish, to determine their cellular source and distribution, and to explore their function. The specific aims would include developing molecular probes to these proteins, in order to determine their structural characteristics and their relationship to one another; characterizing the lipoprotein complexes that the proteins are associated with; identifying the cells that produce or take up the proteins; determining how the proteins change during goldfish optic nerve regeneration; and ascertaining whether they can influence growth and survival of goldfish and mammalian neurons. The goldfish visual system is the subject of this study because this pathway is capable of vigorous regeneration and hence serves as a powerful model for investigating the mechanisms that regulate regeneration. These investigations are expected to lead to techniques for promoting regeneration in the human central nervous system following damage caused by conditions such as spinal cord injury, head injury, stroke, cerebral palsy or neurodegenerative disease.